Phase I Study of the HS-10352 in Patients With Advanced Breast Cancer

NCT ID: NCT04631835

Last Updated: 2022-06-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-08
• Study Completion Date: 2023-08-31

Brief Summary

HS-10352 is a highly potent and selective small molecule inhibitor of phosphoinositide 3-kinase (p110α). In preclinical studies, it demonstrated strong activity against PI3K p110α in vitro and in vivo, and inhibited tumor cell growth. The first-in-human trial is conducted to assess the maximum tolerated dose (MTD) and dose limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of HS-10352 at single dose and multiple doses.

Detailed Description

This is a phase I, open-label, multicenter study to evaluate safety, tolerability, pharmacokinetics, and efficacy of single and multiple doses of oral administration of HS-10352 in patients with locally advanced or metastatic breast cancer with hormone receptor (HR) positive and epidermal growth factor receptor 2 (HER2) negative who have progressed following prior therapy. There is a dose-escalation study, which is designed to evaluate the safety, tolerability, and pharmacokinetics of single dose and multiple doses of HS-10352 given once every day (QD). An alternative dosing schedule of twice every day (BID) may be investigated if the drug clearance of HS-10352 is faster than anticipated.

All patients will be carefully followed for adverse events during the study treatment and for 28 days after the last dose of study drug. Subjects of this study will be permitted to continue therapy with assessments for progression once every 8 weeks, if the product is well tolerated and the subject has stable disease or better. As the disease progresses, survival follow-up is recommended bimonthly.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HS-10352

There are five escalating dose cohorts

Group Type: EXPERIMENTAL

HS-10352

Intervention Type: DRUG

Participants will receive single dose of HS-10352 on Day 1 of Cycle 1 followed by once daily from Day 8 of Cycle 1. (Cycle length: 35 days for Cycle 1 and 28 days for all other cycles). Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Interventions

HS-10352

Participants will receive single dose of HS-10352 on Day 1 of Cycle 1 followed by once daily from Day 8 of Cycle 1. (Cycle length: 35 days for Cycle 1 and 28 days for all other cycles). Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Men or women aged more than or equal to (≥) 18 years, and less than (<) 75 years.

2. HR+ HER2- locally advanced or metastatic breast cancer patients confirmed by histology or cytology for who that standard treatment is invalid, unavailable or intolerable.

3. Patients have at least one target lesion according to RECEST 1.1. The requirements for target lesions are: measurable lesions without local treatment such as irradiation, or with definite progress after local treatment, with the longest diameter ≥ 10 mm in the baseline period (in case of lymph nodes, the shortest axis ≥ 15 mm is required)

4. ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks.

5. Estimated life expectancy greater than (>) three months.

6. Females should be using adequate contraceptive measures throughout the study; should not be breastfeeding at the time of screening, during the study and until 3 months after completion of the study; and must have evidence of non-childbearing potential.

7. Sign Informed Consent Form.

Exclusion Criteria

1. Treatment with any of the following:

1. Previous or current treatment with PI3K, AKT or mTOR inhibitors.

2. Any cytotoxic chemotherapy, investigational agents within 21 days of the first dose of study drug; anticancer drugs which have been received within 14 days before the first administration.

3. Radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study drug, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose.

4. Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.

2. Inadequate bone marrow reserve or organ function.

3. Uncontrolled pleural effusion or ascites or pericardial effusion.

4. Known and untreated, or active central nervous system metastases.

5. History of primary or secondary diabetes.

6. History of acute or chronic pancreatitis

7. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow the study drug that would preclude adequate absorption of HS-10352.

8. History of hypersensitivity to any active or inactive ingredient of HS-10352 or to drugs with a similar chemical structure or class to HS-10352.

9. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

10. Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu Hansoh Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

SUN YAT-SEN Memorial Hospital

Guanzhou, Guangdong, China

Site Status: RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status: RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xichun Hu

Role: CONTACT

xchu2009@hotmail.com

086-021-64175590

Facility Contacts

Herui Yao

Role: primary

Xichun Hu

Role: primary

xchu2009@hotmail.com

086-021-64175590

References

Ouyang Q, Wang Y, Zhang J, Wu Q, Wei H, Li C, Qian X, Hu X. HS-10352 in hormone receptor-positive, HER2-negative advanced breast cancer: A phase 1 dose-escalation trial. Cancer Med. 2023 Dec;12(24):21849-21860. doi: 10.1002/cam4.6755. Epub 2023 Dec 1.

Reference Type: DERIVED

PMID: 38037839 (View on PubMed)

Other Identifiers

HS-10352-101

Identifier Type: -

Identifier Source: org_study_id